Preparation of organic phosphorothioic halides



PREPARATION OF ORGANIC PHOSPHORO- THIOIC HALIDES No Drawing. Application January 20, 1954 Serial No. 405,250

7 Claims. (Cl. 260-461) This invention relates to a method for making phosphorothioic halides. (acid. halides of thiophosphoric acid esters).

The term organic phosphorothioic acids, as used in the specification and appended claims, includes those acidic organic esters of phosphorodithioic acid, phosphorotrithioic acid, and phosphorotetrathioic acid which contain one sulfur atom bonded to a phosphorus atom by a semi-polar bond and one sulfur atom bonded both to a phosphorus atom and a hydrogen atom. The terms also include mixtures of difierent organic phosphorothioic acids.

The phosphoroth-ioic halides have gained wide interest in recent chemistry by virtue of their role as intermediates in the-syntheses of insecticides. 0,0-di-ethyl phosphorothioic chloride is particularly interesting in view of its importance as an intermediate in the preparation of Parathion, a trade name for the product p-nitrophenyl diethylphosphorothionate, which is the principal product of the reaction of 0,0-diethyl phosphorothioic chloride with sodium p-nitrophenate.

It is an object of this invention to provide a method for the preparation of acid chlorides of organic phosphorothioic acids, and especially for the preparation of 0,0-diethyl phosphorothioic chloride. A secondary object is the preparation of certain organic sulfurand nitrogen-containing compounds including thioamides and dithiocarbamates. Still a further object is the conjoint preparation of such organic sulfurand nitrogencontaining compounds and of phosphorothioic chlorides. A still further object is the preparation of compounds which may be used as intermediates in the syntheses of insecticides. Other objects will beaapparent from the following description.

Broadly stated, this invention relates to the process which comprises reacting a hydrogen halide with organic phosphorothioic acids in the presence of at least one nitrogen-bearing hydrogen sulfide acceptor in which a multiple bond exists between adjacent N and C atoms. Examples of the latter are organic nitrogen-bearing hydrogen sulfide acceptors selected from the class consisting of nitriles, organic thiocyanates and aliphatic isothiocyanates.

ORGANIC PHOSPHOROTHIOIC ACIDS EMPLOYED IN THE PROCESS The organic phosphorothioic acids which may be used in the process of this invention can be defined by the structural formula:

RX FS V RX SH f wherein and X' are the same or difie'r'ent elements selected from the class consisting of oxygen and sulfur, preferably those compounds in which X and X' are both oxygen; and R and R' are the same or different organic atent i I 2,822,374 Patented- Feb... 4,, 1,958

2 radicals, preferably hydrocarbon radicals of from 1 to 30 carbon atoms, desirably non-benzenoid hydrocarbon radicals, including the alkyl: and cycloalkyl. radicals, and most desirably alk-yl radicals. Such organic radicals, R and R, are illustrated by the specific examples in the following table:

Table 1 (1) A iphatic radicles, for example:

Alkyl radicles, e.- g.

Methyl Ethyl Propyl (nand iso-) Butyl (n-, sec-, iso-. and tert-) Amyl (n-, sec-, iso-, and tertw) Hexyl radicles, e. g.

n-Hexyl Sec-hexyl 2,2-.di1nethyl:-3-butyl 2.2-dimethyl-4-butyl 2,3-dimethyl-2-butyl 2-n1ethyl-1-pentyl 2-methyl-2-pentyl 3-methyl-1-pentyl Heptyl radicles, e. g.

n-Heptyl Sec-heptyl 2,3-dimethyl-3-pentyl 2, t-dimethyl-2-pentyl 2:41-Jdimei1hyh3mentyl 2,2,3-tr1methyl-3-butyl 3-ethyl-2-pentyl V 2-methyl 2-hexyl, etc;

Octyl radicles, e. g.

n-Octyl 2-ethyl-hexyl Diisobutyl Propenyl radicles, e. g.

Allyl Iso-propenyl Buteny-l radicles, :e. g.--: n-Butenyl-l n-Butenyl-,2 n B1 1tenyl 3 Iso-butenyl Pentenyl radicles, e. g;:

n-Penten-yl-1 n-Pent enylv2 n-Pente|iy.-3 l lex'onyl radicles, e g.

-n-H'exenyl-1 -n- Hexeny1-2, etc. 4,4-dimet-hylfbutenyl-2 *3,4-dimcthyl-butenyl-1, etc. Hentenyl radicles, e. .g. :n-heptenyl Octenyl rad1c1es,'e. g.,:

n-Octenyl Diisobutenyl .Nonenyl radicles, e, g. n-nonenm Deceuy 1.radicles e. g. n-decenyl Dodecenyl radicles, .e. g.

n-Dodecenyl Triisobutenyl V Alkenyl radicles having the formula 'CnHgn-l where nus an integer from 1-8 to 38 inclusive e. g. those derived from parafiin wax, mineral oils, and 4 petrolatum (2)-'Cycloa1iphati' radicles, for example:

Cycloalkyl radicles, e. g

Cyclopentyl, alkylirtedmyolopentyl, .cyclohexyl, and

alkylatedwxclqhQXYlradio g.

nt'yl radicles Mono-and polymefllyb Mono and polyrmethy cyclohexyl radtcles Monoand poly-ethyl-c y'clohex'yl ,radijcles Monoand poly-lso-propyl-cyclohexyl radicles Monoand poly-tert-amyI-cyclohexyl radicles n-Octyl-cyclohexyl radicles Diisobu-tyl-cyolohexyl (i. Ie., tert-octyl-eyclo hexyl) radicles p Nonyl-cyclohexyl radicles Diiso-amyl-cyclohexyl radicles Lauryl-cyclohexyl racllcles Cetyl-cycloh'exyl radicles Naphthenyl radicles Hydroabietyl radicles tures of different f'organic phosphorothioic acids. Although all of such organic phosphorothioic acids are in cluded within the scope of my invention, I prefer to employ the phosphorodithioic acid 0,0-di-esters, commonly referred to as 0,0-di-organo phosphorodithioic acids, because they are cheap and easily available. a

THE HYDROGEN HALIDES EMPLOYED TN THE PROCESS, V

Although, because of its economy, hydrogen chloride is preferred, hydrogen bromide may also be used in the process. Thus the scope of the invention is intended to include hydrogen bromide as well as hydrogen chloride. The hydrogen halide gas may be merelyrbubbled below the surface of a liquid mixture oforganic phosphorodithioic acid and hydrogen sulfide acceptor while maintaining the mixture at a temperature suitable for the reaction to occur.

HDROGEN SULFIDE ACCEPTORS EMPLOYED IN THE PROCESS The mechanism by which this reaction proceeds is not clearly understood, although the molecular structures of the products indicate that the elements of hydrogen sulfide are removed from a combination of one molecule of organic phosphorothioic acid and one molecule of hydro gen halide, and that these elements of hydrogen sulfide then are accepted into the molecular structure of a third compound. This compound may be regarded then as a hydrogen sulfide acceptor, and this terminology is used herein to denote such compounds. Compounds which have been'found to be efiicient hydrogen sulfide acceptors include the hereinbefore mentioned nitriles, organic thiocyanates and aliphatic isothiocyanates. Mixtures of such acceptors may also be used if desired.

Particularly useful hydrogen sulfide acceptors include acetonitrile, acrylonitrile, and benzonitrile; these three are relatively cheap. Additional specific examples of satisfactory hydrogen sulfide acceptors are propionitrile, butyronitrile, benzyl cyanide, ethyl thiocyanate, phenyl thiocyanate, ethyl isothiocyanate, etc. Accordingly to the stoichiometry of the equations below representing the reaction of a hydrogen halide in the presence of a hydrogen sulfide acceptor, the molar ratio of hydrogen sulfide acceptor to phosphorus 'acid should preferably be at least 1 to 1. Greater amounts of hydrogen sulfide acceptor can be employed without detriment and often with benefit to the reaction. Lesser amounts can be used at the expense of optimum yields. In many instances greater amounts are preferred, especially where the hydrogen sulfide acceptor is volatile, as acetonitrile.

PROCEDURE The course of the reaction which produces the organic phosphorothioic halides according to this invention is more fully depicted by the following equations:

in which R and R are the same or ditferent organic radicals described hereinbefore, R" may bethe'same or different from either R, R, X and X may be oxygen or sulfur and A represents one of the halogens, chlorine, and bromine.

In the ordinary practice of this invention the invention may be carried out in any of three different ways:

(1) Hydrogen halide gas is bubbled into an anhydrous solution of the organic phosphorothioic acid at the reflux temperature'and the hydrogen sulfide acceptor is added portionwise.

(2) Hydrogen halide gas is'bubbled into an anhydrous solution of the thiophosphoric acid ester and the hydrogen sulfide acceptor at reflux temperature.

(3) Hydrogen halide gas is bubbled into an anhydrous solution of the hydrogen sulfide acceptor at reflux temperature and the thiophosphoric acid ester is added dropwise.

Each of the above methods gives good yields; method No. 2 is usually the most convenient and simplest, so it is preferred.

The use of a solvent in the reaction described herein provides the advantage of better temperature control, particularly if one of the reactants is a solid and insoluble in the other reactant. Inasmuch as alcohols and water tendto interfere with the desired reaction, it is preferred to use a solvent other than alcohols or water, or even such solvents which tend to produce alcohols or water under the conditions of this type of reaction. Examples of such undesirable solvents are the esters of formic acid, which upon hydrolysis yield alcohols. Thus inert solvents are to be preferred, and particularly those inert solvents which will dissolve hydrogen halides readily. Ethyl ether, dioxane, petroleum ether, chloroform, carbon tetrachloride, tetrahydrofuran, methylene chloride, benzene and carbon disulfide are included among those solvents which are useful for this type of reaction. It is not to be inferred that all inert solvents are equivalent in efiicacy in all cases, but that under certain conditions some inert solvents are more desirable than others. Neither is it to be inferred that a solvent, however advantageous its properties may be, is essential to the success of the reaction in all cases.

Generally the reaction is complete within a period of from two to six hours, although this is dependent, of course, largely upon the rate, at which the hydrogen halide is added to the reaction mixture. But in the case wherein hydrogen chloride is the hydrogen halide used, if the rate at which hydrogen chloride is introduced is moderately vigorous, i. e. in the vicinity of 200 cubic centimeters per minute for areaction mixture whose volume is approximately 200 milliliters, then any other limiting factors do not usually prolong the reaction beyond six hours. If the reaction is allowed to continue beyond six hours, no harmful eifects are observed, however. As the reaction which occurs involves one mole of the organic phosphorothioic acid and one mole of the hydrogen sulfide acceptor, it is desirable, for reasons of economy in carrying out the process, that the starting materials be used in approximately these relative amounts, or with a slight excess of that reactant which is cheaper on a molar basis.

The type of reaction which is the subject of this invention will take place at ordinary temperatures. The speed of the reaction is promoted by heat, however, so the temperature usually employed is approximately that of the boiling point of the refluxing solvent, although it may be higher under conditions of superatmospheric pressure. The process of this invention can be carried out in the broad temperature range of about 10 C. to about 300 C. 7

The following examples illustrate further the details of the invention:

Example I A solution of 37.2 grams (0.2 mole) of 0,0-diethyl phosphorodithioic acid. and 2 g ams .2. mole) Qt ished pressure to yield 28.2 grams (74.8 percent of the theory) of 0,0-diethy1 phosphorothioic chloride. The petroleum ether-insoluble fraction was crystallized from hot benzene, yielding 23.8 grams (86.5 percent of the theory) of thiobenzamide.

Example 2 A solution of 93.0 grams (0.5 mole) of 0,0-diethyl phosphorodithioic acid and 20.5 grams (0.5 mole) of acetonitrile in 200 milliliters of ethyl ether was heated at reflux temperature for four hours, throughout which time a vigorous stream of anhydrous hydrogen chloride gas was led into the solution. The product mixture contained a solid, which was collected on a filter and which constituted a yield of 19.0-grams (51 percent of the theory) of thioacetamide. The ether-soluble fraction was washed successively with 100-milliliter portions of 5 percent aqueous sodium carbonate solution and water, then concentrated and the liquid residue was purified by distillation at reduced pressure to yield 70.0 grams (74 percent of the theory) of 0,0-diethyl phosphorothioic chloride.

Example 3 A solution of 37.2 grams (0.2 mole) of 0,0-diethyl phosphorodithioic acid and 27.0 grams (0.2 mole) of phenyl thiocyanate in IOU-milliliters of low-boiling (30 60 C.) petroleum ether was heated at reflux temperature for four hours throughout which time a vigorous stream of anhydrous hydrogen chloride was led into the solution. The product mixture was allowed to cool, and then was filtered yielding 29.6 grams (87.6 percent of the theory) of phenyl dithiocarbamate. The filtrate was washed successively with 100-milliliter portions of 5 percent aqueous sodium carbonate solution and water, then concentrated and the liquid residue was purified by distillation at reduced pressure to yield 30.2 grams (80.1 percent of the theory) of 0,0-diethyl phosphorothioic chloride.

Example 4 A solution of 37.2 grams (0.2 mole) of 0,0-diethyl phosphorodithioic acid and 17.4 grams (0.2 mole) of ethyl thiocyanate in l-milliliters of ethyl ether was heated at reflux temperature for two hours throughout which time a vigorous stream of anhydrous hydrogen chloride gas was led into the solution. The product mixture was allowed to cool and was diluted with 200 milliliters of low-boiling (3060 C.) petroleum ether. This mixture was stirred well, then filtered. The white solid constituted a yield of 19.8 grams (81.8 percent of the theory) of ethyl dithiocarbamate. The filtrate obtained from the above filtration was washed successively with 100- milliliter portions of 5 percent aqueous sodium carbonate solution and water, then concentrated. The liquid residue was distilled under diminished pressure to yield 30.8 grams (81.7 percent of the theory) of 0,0-diethyl phosphorothioic chloride.

Example 5 A solution of 37.2 grams (0.2 mole) of 0,0-diethyl phosphorodithioic acid and 17.4 grams (0.2 mole) of ethyl isothiocyanate in l00 milliliters of dioxane was heated at reflux temperature for six hours throughout which time a vigorous stream of hydrogen chloride was led into 't'li solution. The c'ooled'p'roduct mtxturewas diluted with 200 'm'illilitersof ethyl ether and the result ing mixture was filtered. The white solid, ethylamine hydrochloride, weighed 10.0 grams (70.0 percent of the theory). The ether-d-ioxane filtrate was washed successively with IOO-millili-ter portions of 5 percent aqueous sodium carbonate solution and water, then concentrated. The liquid residue was purified by distillation under diminished pressure, yielding 24.7 grams (65.5 percent of the theory) of 0,0-diethyl phosphorothioic chloride.

Example 6 The procedure outlined in Example '3 was followed using 42.8 grams of 0,0-diisopropyl phosphorodithioic acid instead of 37.2 grams of 0,0-diethyl phosphorodithioic acid. The yields of phenyl dithiocarbamate and 0,0-diisopropyl phosphorothioic chloride were 28.1 grams (83.1 percent of the theory) and 38.0 grams (88.8 percent of the theory) respectively.

0,0-diethyl phosphorothioic chloride is a colorless liquid with a stale, musty, disagreeable odor. It distills without decomposition at C./ 10 mm. and at 25 0.1 mm. The dithiocarbamates are white solids which may be purified by crystallization from benzene. The thioamides likewise are white solids and these may be purified by crystallization either from benzene, carbon tetrachloride or water depending upon the size and nature of the radicle attached to the thioamide group.

Having thus described my invention by furnishing specific examples thereof, no undue limitations or restrictions should be placed on the scope of my invention except to the extent as defined in the appended claims.

Other modes of applying the principle of the invention may be employed, change being made as regards the details described, provided the features stated in any of the following claims or the equivalent of such be employed.

I therefore particularly point out and distinctly claim as my invention:

1. The method of preparing phosphorothioic halides which comprises reacting a hydrogen halide selected from the class consisting of hydrogen chloride and hydrogen bromide with a phosphorodithioic acid having the structural formula P R10 SH in which R and R are lower alkyl radicals, in the presence of a hydrogen sulfide acceptor selected from the class consisting of R CN, R SCN and R NCS where R and R are selected from the class consisting of lower alkyl and phenyl radicals and R is a lower alkyl radical.

2. The method of claim 1 characterized further in that the hydrogen halide is hydrogen chloride.

3. The method of claim 1 characterized further in that the hydrogen sulfide acceptor is a nitrile having the structural formula R CN in which R is a lower alkyl radical.

4. The method of claim 1 characterized further in that the hydrogen sulfide acceptor is phenyl thiocyanate.

5. The method of claim 1 characterized further in that the hydrogen sulfide acceptor is a lower alkyl isothiocyanate.

6. The method of preparing phosphorothioic chlorides which comprises reacting hydrogen chloride with a phosphorodithioic acid having the structural formula ence of about 1 mole of a hydrogen sulfide acceptor per mole of phosphorodithioic acid, said hydrogen sulfide acs 11 12 ceptor selected from the class consisting of R CN, R SCN References Cited in the file of this patent and R NCS in which R and R are selected' from the FOREIGN PATENTS class consisting of lower alkyl and phenyl radicals and lz is a lower radical i Canada Sept 7. The method of claim 6 characterized further in that 5 OTHER REFERENCES the hydrogen sulfide acceptor is a nitrile having the struc- H k h d f i Chemistry i German),

tural formula R CN in which R is a lower alkyl radical; by Houben-Weyl, 4th ed., No. III, page 672 (1953). 

1. THE METHOD OF PREPARING PHOSPHOROTHIOIC HALIDES WHICH COMPRISES REACTING A HYDROGEN HALIDE SELECTED FROM THE CLASS CONSISTING OF HYDROGEN CHLORIDE AND HYDROGEN BROMIDE WITH A PHOSPHORODITHIOIC ACID HAVING THE STRUCTURAL FORMULA 